tbuckley/cabot-search huggingface dataset:
Abstract 11882: Exploring Abnormalities in Coronary Vascular Resistance Reserve as a Distinct Feature of The Hfpef Syndrome in Women
Authors: Rebecca Crosier, Lisa Mielniczuk, Robert deKemp, Rob S Beanlands, Peter Liu, Thais Coutinho
Journal: Circulation (2022)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is more common in women than men, but mechanisms underlying this female predominance are incompletely understood. Impaired systemic vasodilatory reserve and coronary microvascular dysfunction have been separately described as key abnormalities of HFpEF. However, the coronary vascular resistance reserve (CVRR), defined as the drop in coronary vascular resistance (CVR) from rest to peak stress, and its sex-specific nuances have not been explored in HFpEF. We sought to: (1) determine whether stress CVR differs between HFpEF and controls, and (2) assess sex differences in CVRR in HFpEF. Methods: We performed a cross-sectional study of 32 HFpEF participants and 26 controls, all without obstructive epicardial coronary artery disease. HFpEF was defined according to ESC Guidelines. Dipyridamole stress 82 Rb positron emission tomography was performed, and rest and stress CVR was calculated by dividing mean arterial pressure by coronary flow at rest and stress. Multivariable linear regression assessed (1) the association of HFpEF with stress CVR; and (2) the association of female sex with CVRR in patients with and without HFpEF. Results: Mean age was 74±7 years, 67% were women and mean LVEF was 62±5%: no difference between HFpEF and controls (P&gt;0.05 for each). Results of the multivariable models are summarized in the Image. HFpEF was independently associated with higher global left ventricular CVR at peak vasodilatory stress. In addition, women had lower global left ventricular CVRR as compared to men, and this was unique to women with HFpEF. Results were the same for coronary-specific CVR and CVRR (analyses not shown). Conclusions: To our knowledge, this is the first study to non-invasively explore CVR and CVRR in HFpEF. Our findings suggest increased stress CVR in HFpEF, with a distinct abnormality in CVRR in women with HFpEF. Abnormal CVRR in women may contribute to the female predominance of HFpEF.
Abstract 11805: Giant Cardiac Lymphangioleiomyomatosis: A Previously Unreported Primary Cardiac Tumor
Authors: Kun Xiang, Chengming Fan
Journal: Circulation (2022)

Lymphoangioleiomyoma is a benign lymphatic tumor characterized by proliferation of perivascular epithelioid cells and is commonly known as part of the lymphangioleiomyomatosis (LAM). LAM is a rare, slowly progressive systemic disease and is considered as a low-grade, metastatic neoplasm, almost exclusively affects women of child-bearing age. LAM generally presents with features of cystic lung destruction. Independent onset of extrapulmonary LAM without typical cystic lung destruction is very rare. Herein, for the first time, we present a giant primary cardiac lymphangioleiomyoma of a 24-year old man with exertional dyspnea and intermittent chest pain. A giant mass (52 mm х 65 mm) and multiple irregular dark purple cauliflower-like nodules were found with irregular margins and firm texture involving the right atrium, right ventricle, inferior vena cava, superior vena cava and sinus node (Attached figure). Given the large size and wide involvement of the heart tumors, radical surgery was not performed except for a tissue biopsy. The final diagnosis of cardiac lymphangioleiomyoma was defined after pathological reexamination of the tumoral tissue sample. After comprehensive communication, the patient refused further surgical treatment and discharged with waiting for heart transplant. To our knowledge, the presented cardiac lymphangioleiomyoma is the first to be reported in the literature.
Abstract 11809: Role of Computed Tomography-Based Evaluation of Skeletal Muscle Area in Predicting Cardiovascular Outcomes in Patients With Chronic Heart Failure Following Cardiac Resynchronization Therapy
Authors: Taisuke Harada, Hidekazu Kondo, Kunio Yufu, Masaki Takahashi, Yumi Ishii, Ichitaro Abe, Hidefumi Akioka, Tetsuji Shinohara, Yasushi Teshima, Naohiko Takahashi
Journal: Circulation (2022)

Introduction : Sarcopenia, defined as skeletal muscle depletion, has been associated with poor cardiovascular outcomes in patients with chronic heart failure (CHF). Hypothesis : This study aimed to determine possible associations between sarcopenia and poor cardiovascular outcomes in patients with CHF after cardiac resynchronization therapy (CRT). Methods: This retrospective study evaluated 120 patients who underwent CRT implantation between March 2004 and June 2018. Only 58 patients who underwent computed tomography (CT) within 30 days of CRT were eligible for inclusion, and their data were analyzed (25 women; 33 men; mean age, 71.6 ± 8.7 years). The skeletal muscle area was measured at the third lumbar vertebra, and the skeletal muscle index (SMI) was calculated (Figure 1). Major adverse cardiovascular events (MACE) included cardiovascular death, hospitalization due to heart failure, cerebral infarction, acute myocardial infarction, and cardiac arrest. Results: During the follow-up period (mean, 868 ± 617 days), MACE occurred in 22 of 58 patients (38%). The patients were allocated to two groups according to sex-based tertiles of SMI. The lowest tertile was defined as the low SMI group. Kaplan-Meier survival analysis demonstrated that the low SMI group had a greater incidence of MACE (log-rank 4.38; P = 0.036, Figure 2). Cox proportional hazards regression analysis also revealed that low SMI was significantly associated with MACE (hazard ratio 3.08; 95% CI: 1.26-7.66, P = 0.014). Conclusions: Decreases in SMI on CT imaging may predict the occurrence of MACE in patients with CHF who underwent CRT.
Abstract 11802: Hypocretin/Orexin Receptor-2 Influences Mortality Risk After Myocardial Infarction
Authors: Peter Wohlfahrt, Dominik Jenca, Dana Dlouhá, Vojtech Melenovsky, Petr Jarolim, marek sramko, Martin Kotrc, Michael Zelizko, Jolana Mrazkova, Jan Pitha, Vera Adamkova, Josef Kautzner
Journal: Circulation (2022)

Introduction: Hypocretin/orexin system has been shown to play a role in heart failure. Whether this system also influences all-cause mortality in patients after myocardial infarction (MI) is unknown. The aim of the present study was to evaluate the effect of rs7767652 allele variants, upstream of hypocretin/orexin receptor-2, on prognosis of patients with MI. Methods: Data from a single-center prospectively designed AMBITION registry of consecutive patients hospitalized for MI at a large tertiary cardiology center were analyzed. Patients with type I MI, without previous history of MI or heart failure were included. A random population sample including 1,953 individuals was used to compare allele frequencies in the population. Results: Out of 1,593 patients in the registry, 1,009 fulfilled the inclusion criteria. In total, 6.1% patients were homozygotes and 39.4% heterozygotes for the minor allele. Allele frequencies in patients with MI did not differ from the general population (χ 2 p=0.62), suggesting no influence on the MI risk. During the median follow-up of 27 months (IQR 13-41), mortality rate was 8.4%. Homozygotes for the rs7767652 minor allele had a higher mortality risk as compared to heterozygotes (p=0.001) and homozygotes for the major allele (p=0.001) ( Figure ). After multivariate adjustment, minor allele homozygotes remained at increased mortality risk (HR 2.83, 95% CI 1.55-5.19). Minor allele homozygotes experienced more often ventricular fibrillation (12.9% vs. 4.8%, p=0.01) and required more often CPR (16.1% vs. 7.0%, p=0.02). Among patients with EF&lt;40% at hospital discharge, minor allele homozygotes had a lower increase in EF during the follow-up (2.5±11.0 vs. 8.4±9.4, p=0.04). Conclusions: Our Mendelian randomization study shows that hypocretin/orexin system influences prognosis of patients with MI. This effect may be partially explained by the increased arrhythmic risk and the effect on the left ventricular systolic function recovery.
Abstract 12698: Alert-Driven versus Scheduled Remote Monitoring of Implantable Cardiac Defibrillators: An Economic Analysis From the Trust Randomized Trial
Authors: Derek S Chew, Jonathan P Piccini, FLora Au, Camille Frazier-Mills, Justin Michalski, Niraj Varma
Journal: Circulation (2022)

Introduction: Current implementation of remote patient monitoring (RPM) for implantable cardioverter defibrillators (ICDs) involves a hybrid of remote assessment and in-person evaluation (IPE) every 3 months. Alert-driven RPM or fully virtual care without routine visits may reduce non-actionable patient evaluation, increased clinic workload and inefficient resource allocation. Objective: To conduct a cost-consequence analysis to compare three patient management strategies following ICD implantation: (a) IPE only, (b) RPM-conventional (hybrid of IPE and RPM), and (c) RPM-alert (alert-based ICD follow up). Methods: We constructed a decision-analytic Markov model to estimate the costs and benefits of three strategies of patient management following ICD implantation over a two-year time horizon from the perspective of the US healthcare system. Aggregate and patient-level data from the TRUST (Lumos-T Safely RedUceS RouTine Office Device Follow-up) clinical trial informed clinical effectiveness model inputs. TRUST randomized 1339 patients 2:1 to conventional RPM or IPE alone, and found that RPM was safe and reduced the number of non-actionable encounters. Cost data was obtained from the published literature. The primary outcome was incremental cost. Results: The mean cumulative costs per patient were $12,688 in the IPE group, $12,001 in the RPM-conventional group, and $11,011 in the RPM-alert group. Compared to the IPE group, both the RPM-conventional and RPM-alert groups were associated with lower incremental costs of -$687 (95% confidence interval (CI)-$2,138 to +$638) and -$1,677 (95% CI -$3,134 to -$304), respectively. Of the three groups, the RPM-alert strategy was the most cost-effective strategy with an estimated cost-savings in 99% of simulations. Conclusions: Alert-driven RPM was economically attractive and, if patient outcomes and safety are comparable to conventional RPM, may be the preferred strategy of patient follow up.
Abstract 11823: Are Disease-Specific Patient-Reported Outcomes Measures (PROMs) Used in Cardio Genetics? A Review
Authors: Sarah Van Pottelberghe, Nina Kupper, Esther Scheirlynck, A.S. Amin, Edward Callus, Ruth Biller, Nynke Hofman, Julie Nekkebroeck, Sonia Van Dooren, Frederik Hes, Arthur A Wilde, Saskia van der Crabben
Journal: Circulation (2022)

Background: Besides hard medical outcomes in patients with inherited cardiac conditions (ICC). it is crucial to focus on the patient-reported outcomes (PRO) as well. These patients may have a disease-specific need due to ICC-related distress concerning family members and reproductive choices. We evaluated which PRO scales are currently used in cardiogenetics. Methods: From three datasets (PubMed, PsychINFO, and Web of Science), eligible studies published between 2008-2022 were selected as described in the review protocol (PROSPERO 2021 CRD42021271384). The quality of studies was assessed (https://pubmed.ncbi.nlm.nih.gov/27082055 ) and analyzed for the primary outcome variable of patient-reported outcomes. Results: Eighteen out of 232 articles were selected for data extraction; 9 studies used a cross-sectional design, and population characteristics and outcome measures varied. The risk of bias was high or unclear in 77% of the studies. All studies mainly used two questionnaires in combination or alone: the short form of medical outcomes survey (SF-36), a generic PROM that reports on health status and the Hospital Anxiety and Depression Scale (HADS), a standard measure of psychological well-being. Thirteen studies using SF-36 showed lower scores on the mental health component in patients with ICC versus population norms. Ten studies using HADS showed a prevalence of clinically significant anxiety (17-47%) and depression (8.3% to 28%) which are higher than the population norm (8.3% and 6.3%). Conclusion: Our results from only a few published studies indicate that although psychological morbidity in ICC patients is high, measurements are non-specific, variable, and generic and address overall health, instead of addressing factors specific to ICC, such as heritability. We propose to develop a disease-specific PROM for cardiogenetics to evaluate the heritability factor in patients with ICC to implement in the care pathway and optimize patient-centred care.
Abstract 12723: The Tendyne Valve: A Novel Approach to Mitral Valve Replacement
Authors: Neal Shah, Christiane Haeffele, Rahul Sharma, Mirela Tuzovic
Journal: Circulation (2022)

Clinical Presentation: 64-year-old female with history of CAD with STEMI s/p PCI of RCA, HFrEF (45%), afib, HTN, DM2, severe MR and moderate calcific MS presented with shortness of breath found to have recurrent CHF. She was not amenable to surgical valve replacement and standard transcatheter percutaneous options are limited given the significant MAC. Tendyne (Abbot) transcatheter mitral valve implantation (TMVI) is an experimental minimally invasive option to treat significant MR with challenging mitral anatomy. Patient underwent a minimal apical thoracotomy via TEE guidance, placement of delivery catheter and valve deployment followed by an apical tether to maintain adequate tension. Post-deployment, there was no significant MR, MS or LVOT obstruction. Imaging Findings: See Image. Discussion: TEE is critical from pre-procedure planning to device implant and post-procedural monitoring. Pre-procedural planning requires accurate understanding of the mitral valve anatomy. During the trans-apical thoracotomy, TEE is essential in confirming correct puncture site to ensure appropriate delivery catheter position. Once appropriately positioned, evaluation via color doppler nad 3D are necessary to evaluate device seating, residual regurgitation and LVOT obstruction. Once apical cap is tethered into apex, the valve is re-visualized on TEE to ensure appropriate valve tension prior to closure of thoracotomy. Conclusion: TENDYNE TMVI is a reasonable option to consider for patients with significant MR and challenging mitral anatomy and not an open surgical candidate. TEE imaging is critical to optimize valve implantation both pre-procedural and post-procedural.
Abstract 11858: ATIC-Mediated De Novo Purine Synthesis Protects Endothelial Cells From Disturbed Flow-Induced Injury in Atherosclerosis
Authors: Qian Ma, Qiuhua Yang, Sudhahar Varadarajan, Tohru Fukai, David Fulton, Yuqing Huo
Journal: Circulation (2022)

Aims: Disturbed flow at arterial bifurcations and curvatures of blood vessels, combining with other atherosclerotic risk factors, promotes endothelial cell (EC) DNA damage and the subsequent EC death, compromises the integrity of the endothelial barrier and ultimately leads to the formation of atherosclerotic lesions. ECs reprogram their metabolism to protect them from atherogenic injury induced by disturbed flow. De novo purine synthesis (DNPS) has been reported to regulate DNA repair and cell proliferation in cancer cells, however, its role in atherosclerosis has not been determined. 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (ATIC) is the enzyme that catalyzes last two steps of DNPS. We investigated the role of ATIC-driven DNPS in flow-induced EC metabolic reprogramming and in the development of atherosclerosis. Methods and Results: The expression of DNPS and DNA damage associated genes in ECs exposed to disturbed flow were assessed by analyzing the published RNA-Seq datasets. ATIC protein expression and DNA damage were examined in the endothelium at atheroprone regions of mouse aortas. Mice with EC-specific Atic knockout were utilized to investigate the role of endothelial ATIC in atherosclerosis. ATIC-mediated DNPS were increased in ECs exposed to disturbed flow both in vitro and in vivo , which was highly associated with the increased DNA damage response. EC-specific Atic knockout enhanced DNA damage of ECs, EC apoptosis, EC permeability and the subsequent formation of atherosclerotic lesions. Conclusion: Enhanced ATIC-mediated DNPS in ECs exposed to disturbed flow supplies purine nucleotides to repair DNA damage and to preserve EC barrier integrity in vulnerable atheroprone regions, and ultimately protects against the development and progression of atherosclerosis.
Abstract 11801: Glycoprotein Nonmetastatic Melanoma Proteinbbregulates Lysosomal Integrity and Lifespan of Senescent Endothelial Cells
Authors: Chien Lun Hsiao, Masayoshi Suda, Goro Katsuumi, Ippei Shimizu, Yohko Yoshida, Takaaki Furihata, Ryo Furuuchi, Tohru Minamino, YUNG TING HSIAO
Journal: Circulation (2022)

Introduction: The accumulation of senescent cells during aging relates to the development of various age-related pathologies including atherosclerosis and heart failure, which can be improved by specific elimination of senescent cells, so called “senolysis”. We have identified glycoprotein nonmetastatic melanoma protein B (GPNMB) as an antigen specifically expressed by senescent endothelial cells, so called “seno-antigen”. Also, we previously developed the vaccine against Gpnmb, eliminated senescent cells in mice, leading to an improvement of age-related pathologies. However, detailed function of GPNMB in senescent cells is still uncertain. Purpose: To elucidate the role of GPNMB in senescent cells and cardiovascular-related pathologies. Methods: Overexpression or depletion of GPNMB in endothelial cells (ECs) were generated. Cellular senescence was induced in ECs by doxorubicin. Gpnmb-knockout or overexpressed (Gp-KO or Gp-OE) mice were generated and imposed to hind-limb ischemia treatment or high-fat-diet feeding to evaluate vascular functions. Double transgenic mice (ApoE-KO and Gp-KO or Gp-OE) were also generated and imposed to high-fat diet to develop atherosclerosis. Results: The depletion of GPNMB in ECs was proved to shorten their replicative lifespan, and increase the expression of negative cell cycle regulators including p53, p21 and p16. Conversely, overexpressed GPNMB protected ECs from senescence stress. In vivo studies showed the impairment of vascular function, atherogenesis, and endothelium-dependent vasodilatation were enhanced in Gp-KO mice, but attenuated in Gp-OE mice. Furthermore, GPNMB was found to localize on lysosomal membrane. Cells with depleted GPNMB demonstrated the accumulation of dysfunctional lysosomes, indicated the contribution of GPNMB in maintaining lysosome integrity. Under senescence-associated lysosomal stress, elevated GPNMB expression was detected, contributing to senescent cells survival. Conclusions: GPNMB acts as a protective factor to senescent cells. Seno-antigen targeting GPNMB is possibly considered as an efficient strategy against cardiovascular diseases and other age-associated disorders with higher selectivity and fewer off-target effects.
Abstract 12687: Race, Resilience, and Health Literacy Are Important to Medication Adherence in Those With Heart Failure
Authors: Rebecca Meraz, Jocelyn McGee, Elizabeth Perry, Weiming Ke, Kathryn A Osteen
Journal: Circulation (2022)

Background: Personal and psychological factors, such as depression, have a considerable influence on nonadherence to medications and self-care in those with heart failure. More evidence, however, is needed about positive personal factors that motivate adherence to medications and self-care in those with heart failure. Objective: The purpose of this study was to investigate whether there was a consistent and predictable relationship between the personal resources of resilience, hope, health literacy, social support, and self-care activation and adherence to medications and HF self-care and whether race impacts adherence. Methods: This study used a prospective, cross-sectional design. Correlation and multiple regression analyses were used to estimate associations between study variables. A nationwide, diverse sample was recruited for this study. Results: Of the 174 participants, 51% were female, 48% were persons of color (POC) and the mean age was 62 years. Medication adherence and health literacy were significantly lower among POC compared to Whites. POC were more likely to be under 65 years, single, and have a lower income. Following adjustment for differences in age and depressive symptoms, a predictive relationship remained between resilience (B = -0.049, p &lt; 0.001), health literacy (B = -0.258, p = 0.003) and medication adherence. A high level of perceived social support (B = 5.359, p &lt; 0.001) was a predictor of better HF self-care. Conclusion: Persons with heart failure may have better medication adherence and overall self-care if sufficiently resilient, health literate, and supported regardless of their degree of hope or activation. Race and age may be important factors to consider. More research is needed to understand the relationship between resilience and medication adherence.
Abstract 12717: Understanding and Addressing the Unique Challenges of Heart Failure Management in Older Adults
Authors: Susan D'Anna, Margaret Emmons, Deborah Cantlin, Mohammadtokir Mujtaba, Lauren Gilstrap
Journal: Circulation (2022)

Introduction: The heart failure (HF) population is aging. As patients age, certain aspects of HF care become more and less challenging. The aim of this qualitative study is to understand which aspects of HF care are the most challenging for older adults and identify potential solutions and coping strategies. Methods: We conducted semi-structured interviews with 41 patients ≥75 years old with HF. The oldest was 93 years old and the youngest was 75 with an average age of 82. Interviews were conducted in both the inpatient (n=23) and outpatient/clinic (n=18) settings. Patients were asked a series of 3 questions focused on care challenges, effective strategies and coping mechanisms. Interviews were recorded and transcribed. Recordings were listened to while reviewing the transcripts, then analyzed and coded for thematic analysis. Results: Older patients with HF identified: “salt/fluid restrictions,” “exercise limitations,” “medication compliance” and “transportation for visits” as key challenges of HF management. Effective strategies identified included: “family support,” “pill boxes and logbooks to help me remember” and “the socialization of cardiac rehab.” Successful coping strategies included: “family,” “religion” and “motivation to maintain independence.” Discussion: Older patients with HF face many of the same challenges as younger patients but also face additional hardships with transportation, cognitive limitations and social isolation ( Figure 1 ). These challenges are worse for older adults without family support. A desire to remain independent is a significant motivating factor for older adults with HF. Understanding these challenges and motivations can inform care plans better tailored to the care of older adults with HF.